(a) Field of the Invention
This invention relates to cyclic alkylidenyl anilinomethylenemalonates, to a process for their preparation and to a process for converting them to known 3-quinolinecarboxylic acids useful as antibacterial agents.
(B) Description of the Prior Art
The term "pyridyl" used in the following presentation of the prior art has the same meaning as "pyridinyl", the preferred term now used in Chemical Abstracts and used hereinbelow in describing the instant invention.
The Lesher and Carabateas U.S. Pat. No. 3,753,993, issued Aug. 21, 1973, and U.S. Pat. No. 3,907,808, issued Sept. 23, 1975, show the preparation of 1,4-dihydro-1-(lower-alkyl)-4-oxo-7-(pyridyl)-3-quinolinecarboxylic acids, antibacterial agents, by reacting the corresponding 1,4-dihydro-4-oxo-7-(pyridyl)-3-quinolinecarboxylic acid or lower-alkyl ester with an alkylating agent, e.g., lower-alkyl halide, sulfate or sulfonate. These patents also show the preparation of the intermediate 1,4-dihydro-4-oxo-7-(pyridyl)-3-quinolinecarboxylic acids and lower-alkyl esters by reacting di-(lower-alkyl) ethoxymethylenemalonate with a 3-(pyridyl)aniline. Also shown are the preparations of the intermediate 3-(pyridyl)anilines, e.g., 4-(3-aminophenyl)-pyridine [same as 3-(4-pyridinyl)aniline] by reducing the corresponding 4-(3-nitrophenyl)pyridine and 4-(3-aminophenyl)-2-ethylpyridine by catalytically hydrogenating 2-chloro-6-ethyl-4-(3-nitrophenyl)pyridine.
The Lesher U.S. Pat. No. 3,563,981, issued Feb. 16, 1971, shows the preparation of various cyclic alkylidenyl Ar-aminomethylenemalonates, where Ar is an aromatic radical having one or two aromatic rings which can be benzenoid or 5- or 6-membered heteroaromatic, by reacting the appropriate aromatic amine with a mixture of a trialkyl orthoformate or trialkyl orthoacetate and a cyclic alkylidenyl malonate. Cyclic alkylidenyl anilinomethylenemalonates derived from anilines are converted by heating to 4-hydroxyquinolines having no substituent in the 3-position. This patent also shows that cyclic isopropylidenyl N-(lower-alkyl)anilinomethylenemalonates derived from N-(lower-alkyl)anilines did not undergo cyclization.
The Kohjin Co. Ltd. Japanese Provisional Patent Publication No. 50-100064/75, published Aug. 8, 1975 and based on Application No. 49-6071/74, filed Jan. 11, 1974, discloses that 6-ethylamino-2-picoline can be prepared by reducing 6-acetamido-2-picoline with lithium aluminum hydride. No experimental details are given for preparing 6-ethylamino-2-picoline, but it appears that the reduction of 6-acetamido-2-picoline with lithium aluminum hydride most likely would produce a mixture of the final product, some starting material, and probably one or more ring-hydrogenated by-products.